Intratumor administration of beta-interferon in recurrent malignant gliomas. A phase I clinical and laboratory study.
We administered doses of 5 to 180 x 10(6) IU of beta-serine-interferon (IFN-beta ser17) twice weekly to 20 patients with recurrent malignant gliomas in a Phase I study. Interferon was given through an Ommaya reservoir connected by a catheter to the tumor cavity. Side effects of interferon therapy occurred in only one patient and consisted of nausea, vomiting, fever, and chills after each treatment, presumably due to rapid diffusion of interferon into ventricular cerebrospinal fluid (CSF). Problems with the Ommaya reservoir (obstruction in two patients and infection in four patients) led to six patients being terminated from the study, and represent the major difficulty with this form of therapy. Although this was primarily a study of interferon toxicity, of 12 evaluable patients, 3 had stable disease for 148, 192, and 539 days; 9 had progressive disease. In addition, we tested the effect of IFN-beta ser17 on the growth of early passage in vitro cultures of malignant gliomas established from patients. Growth inhibition varied from 0% to more than 50%. In all cultures evaluated, the combination of recombinant gamma-interferon plus IFN-beta ser17 enhanced growth inhibition. Further clinical and laboratory study is necessary to better define the therapeutic efficacy of IFN-beta ser17 and the role of combinations of interferons in the treatment of malignant gliomas.
Fetell
M R
MR
Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, New York.
Housepian
E M
EM
Oster
M W
MW
Cote
D N
DN
Sisti
M B
MB
Marcus
S G
SG
Fisher
P B
PB
D000328:Adult; D000368:Aged; D004341:Drug Evaluation; D005260:Female; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta; D008297:Male; D008577:Meningeal Neoplasms / Q000628:therapy; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007370:Interferon Type I; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a